The prelimbic cortex (PrL) as a part of the medial prefrontal cortex (mPFC) plays a crucial role in drug addiction. Previous studies have shown that glutamatergic transmission through the NMDA and AMPA receptors plays an important role in morphine rewarding properties. In this study, we evaluated the effect of glutamate receptors blockade within the PrL on morphine self-administration. Male Wistar rats were randomly selected and divided into 7 groups. Trained rats were placed in self-administration apparatus, where they pressed an active lever for receiving morphine (5 mg/mL) in test groups and saline in saline group during 11 consecutive days for 2 h per session. The effects of intra-prelimbic AMPA receptor antagonist (CNQX; 0.5 and 2.5 μg/0.5 μL) and the NMDA antagonist (AP5; 0.1 and 1 μg/0.5 μL) on self-administration were tested. Our results demonstrated that intra-prelimbic injection of different doses of CNQX and AP5, and co-administration of these 2 drugs before self-administration significantly decreased active lever pressing compared with morphine group (p < 0.001). Also, the number of self-infusion significantly decreased in test groups compared with morphine group (p < 0.001). These findings suggest that a reduction in PrL glutamatergic output can modulate morphine reinforcement.
Background:The attitude of research on addiction has been done on the key role of glutamate. As a regard, the prelimbic cortex (PrL) has an important role in addiction, learning, and memory. We tried to investigate the level of glutamate and aspartate concentration after glutamate receptors blockade in this region in the morphine-addicted rats.Materials and Methods:In this study, we examined the effects of local infusion of the N-methyl-D-aspartate receptor and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonists, 2-amino-5-phosphonovaleric acid (AP5), and 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), into the PrL cortex on the level of excitatory amino acids (EAAs) and glycine. After 11 days of self-administration, the prelimbic area of the brain was taken out, and the EAAs and glycine concentration was measured by high-performance liquid chromatography.Results:Morphine resulted in the significant increase in the EAAs concentration within this area (P ≤ 0.001). Microinjection of AP5 into this region before using of morphine significantly decreased the morphine-induced glutamate and aspartate concentration (P ≤ 0.001). CNQX had the same effect and significantly reduced the EAAs concentration compared to the morphine group (P ≤ 0.001). In addition, microinjection of AP5 and CNQX simultaneously increased glycine concentration (P ≤ 0.001).Conclusions:These results show that morphine stimulates the EAAs release in the prelimbic area. It seems that microinjection of AP5 or CNQX in this region is effective in reducing morphine-induced EAA. It is suggested that EAA transmission in the PrL cortex may be a possible target for treatment of morphine addiction.
Background: Galanin is an orexigenic agent and has been demonstrated to be a putative regulator of gonadotropin secretion. It is well known that this orexigenic peptide probably plays a vital role in the regulation of reproduction; however, the underlying mechanisms have not been fully elucidated. Objectives: The goal of this study was to determine the role of galanin in the regulation of gonadotropins in goats, which were subjected to either high or low energy diets. Materials and Methods: Adult female Saanen goats were randomly divided into 2 groups. Animals in the two groups were fed either a 100% or a 150% energy content diet, respectively, for a month. On the first day of the experiment, all animals received an intravenous injection of 1 µg galanin/kg body weight. On the second day, each animal was administered 2 µg galanin/kg body weight. Blood samples were withdrawn by jugular venipuncture at 30-minute intervals, 3.5 h before and 3.5 h after galanin injection. In order to determine the concentration of LH and FSH, plasma was isolated and subjected to radioimmunoassay in order to determine the concentrations of relevant gonadotropin hormones. Results: The intravenous administration of 1 µg galanin/kg body weight to goats who were subjected to a high-energy feed significantly reduced circulating LH and FSH levels. It contrast, this dose had no effect on goats subjected to the lower energy diet. The injection of galanin at a dose of 2 µg/kg body weight had no influence on mean plasma concentrations of gonadotropins in goats fed either of the two diets. Conclusions:The results indicate that galanin is not a principal hypophyseal regulator in the secretion of gonadotropins in Saanan goats. It may be inferred that in the same animal model galanin has a gonadotropin-reducing effect when its in vivo concentration increases.
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